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The FDA is set to make a call on Aug. 14 on whether to approve seladelpar for the treatment of primary biliary cholangitis. Three months after spending $4.3 billion on CymaBay Therapeutics for its primary biliary cholangitis (PBC) med, Gilead Sciences has presented a fresh slice of data as a reminder of seladelpar’s potential while an FDA decision is pending. The open-label ASSURE study comprised 174 patients who had already previously participated in another study of seladelpar and who had not responded adequately to ursodeoxycholic acid (UDCA), the typical treatment for PBC. They received an oral dose of 10 mg seladelpar each day, with nearly all patients being female and also receiving UDCA treatment. A total of 148 patients completed 12 months of treatment. Of these, 70% reached the clinically meaningful composite response endpoint, Gilead explained in a presentation of the interim data in a May 18 release. Across all patients who received seladelpar, 37% experienced an average change from baseline alkaline phosphatase (ALP) level of 44%, considered a return to normal levels. Twenty patients received the selective PPAR-delta agonist for a full two years. Of these, 70% reached the response endpoint, but only 25% saw ALP normalization. Other biomarkers of liver injury were also reduced. Specifically, total bilirubin fell by 9%, gamma-glutamyl transferase by 36% and alanine aminotransferase by 25% from baseline levels. There were no treatment-related adverse events, while 4.6% of patients discontinued due to adverse events, Gilead reported. “The initial data from ASSURE further support the efficacy and safety profile of seladelpar observed across the robust development program and continue to indicate that seladelpar has the potential to be a best-in-class therapy that could help transform treatment for people living with primary biliary cholangitis,” Gilead Chief Medical Officer Merdad Parsey, M.D., Ph.D., said in the release. “The PBC community has been waiting for new treatments that help slow the progression of their liver disease as well as address difficult symptoms like pruritus that can have a significant impact on their quality of life,” Parsey added. “We are excited to offer a new option for this community as we work to bring seladelpar to people living with PBC, if approved.” Seladelpar was submitted to the FDA to treat PBC with pruritus, or itching, without cirrhosis or with compensated cirrhosis in December 2023. The rare liver disease primarily affects women over 40 and is characterized by impaired bile flow and the accumulation of bile acids in the liver, causing an elevation of liver enzymes that can be dangerous. The FDA is set to make a call on Aug. 14 on approving seladelpar for the treatment of PBC, including pruritus, in adults without cirrhosis or with compensated cirrhosis who are inadequate responders or intolerant to UDCA.

Mabwell (Shanghai) Bioscience is an innovative biopharmaceutical company with a full industrial chain layout that has developed multiple Antibody-Drug Conjugate (ADC) technology platforms. The company primarily focuses on oncology and age-related diseases, encompassing therapeutic areas such as cancer, autoimmune disorders, metabolism, ophthalmology, and infections. At the upcoming ASCO conference, the company will present the Phase I/II clinical study results of 9MW2821 for several advanced solid tumors through an oral report. 9MW2821 employs a site-specific linker-coupling technology developed in collaboration with the Shanghai Institute of Materia Medica, Chinese Academy of Science. This technology couples the MMAE toxin and, through optimizations in the coupling process, addresses common issues such as linker mismatches, avoiding problems like ADC aggregation for enhanced stability. The antibody is humanized and optimized for post-translational modifications (PTM), with a drug-to-antibody ratio (DAR) of 4. In February 2024, 9MW2821 was granted "Fast Track Designation" (FTD) by the FDA for treating advanced, recurrent, or metastatic esophageal squamous cell carcinoma. It is currently the first targeted therapy against Nectin-4 globally to reveal clinical efficacy and safety data for indications of esophageal and cervical cancer. Currently, four clinical trials involving 9MW2821 have been initiated: 1.An open, multicenter Phase I clinical study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of 9MW2821 in patients with advanced solid tumors, with plans to enroll 40 patients. 2.A Phase I/IIa clinical trial to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of 9MW2821 in patients with advanced solid tumors, aiming to enroll 208 patients. 3.An open, single-arm, multicenter Phase Ib/II clinical study of 9MW2821 combined with Junshi Biosciences' PD-1 monoclonal antibody, Toripalimab, evaluating safety and efficacy in patients with advanced or metastatic urothelial carcinoma, with plans to enroll 100 patients. 4.A randomized, open, controlled, multicenter Phase III clinical study comparing 9MW2821 in patients with locally advanced or metastatic urothelial carcinoma who have previously undergone chemotherapy that included platinum agents and PD-(L)1 inhibitors but are ineligible for surgical resection, planning to enroll 420 patients. Urothelial Carcinoma (UC) As of April 27, 2023, in 18 UC patients who progressed following treatment with platinum-based chemotherapy and immune checkpoint inhibitors, the dose of 1.25 mg/kg showed an Objective Response Rate (ORR) and Disease Control Rate (DCR) of 55.6% and 94.4%, respectively. As of December 5, 2023, 9MW2821 at a dose of 1.25 mg/kg in a phase II clinical trial showed ORR and DCR of 62.2% and 91.9% respectively, in the monotherapy treatment of advanced urothelial carcinoma patients. The median Progression-Free Survival (PFS) was 6.7 months, and the median Overall Survival (OS) had not yet been reached. Currently, the phase III clinical study 9MW2821-2023-CP301 of 9MW2821 monotherapy for locally advanced or metastatic urothelial carcinoma patients who have been previously treated with platinum-based chemotherapy and PD-(L)1 inhibitors has officially commenced. Furthermore, the phase I/II clinical study 9MW2821-2023-CP104 combining 9MW2821 with a PD-1 inhibitor is also progressing, with the first subject successfully enrolled. Cervical Cancer (CC)On March 16, 2024, MyWay Biotech reported positive clinical study results for their first cervical cancer study targeting Nectin-4 with an antibody-drug conjugate (ADC) at the 2024 SGO conference (First positive cervical cancer results for Nectin-4, MyWay announces clinical study 9MW2821). The Phase I/II cervical cancer cohort of 9MW2821 included patients with Nectin-4 positive recurrent or metastatic cervical cancer, who have failed platinum-based doublet chemotherapy with or without bevacizumab (a VEGF monoclonal antibody), and have been treated with no more than two lines of systemic therapy. As of September 25, 2023, within the expanded cervical cancer cohort of this study, the detection rate for Nectin-4 expression was 89.67%, with a 3+ tumor cell staining intensity detection rate of 67.82%. This cohort enrolled a total of 40 patients, with 57.5% of the participants previously treated with platinum-based doublet chemotherapy combined with bevacizumab, and 60% of participants previously having received platinum-based chemotherapy and immune checkpoint inhibitors. In terms of efficacy, under the selected dosage of 1.25 mg/kg in Phase II, the objective response rate (ORR) and disease control rate (DCR) among 37 evaluable patients were 40.54% and 89.19% respectively, with 1 case of complete response (CR, 2.70%), 14 cases of partial response (PR, 37.84%), and median progression-free survival (mPFS), median overall survival (mOS), and median duration of response (mDOR) not yet reached. Among patients with Nectin-4 3+ expression, the ORR and DCR for 26 evaluable patients were 50.00% and 92.31% respectively. For patients previously treated with platinum-based chemotherapy and immune checkpoint inhibitors, the ORR and DCR among 21 evaluable patients were 38.10% and 85.71%, respectively. Esophageal Squamous Cell Carcinoma (ESCC)As of February 20, 2024, in the phase II clinical trial of 9MW2821 at a dosage of 1.25 mg/kg, among 30 patients with advanced esophageal cancer who received monotherapy and completed at least one tumor efficacy evaluation, the objective response rate (ORR) and disease control rate (DCR) were 30% (9/30) and 73.3% (22/30), respectively. The phase II clinical study targeting esophageal cancer indications will continue to enroll and evaluate patients and will initiate phase III clinical discussions as soon as possible. In February 2024, 9MW2821 was granted Fast Track Designation (FTD) by the FDA for the treatment of advanced, recurrent, or metastatic esophageal squamous cell carcinoma (This is the first Nectin-4 ADC showing positive results for ESCC; 9MW2821 received FTD from the FDA). SafetyClinical trial results for 9MW2821 targeting advanced solid tumors were orally presented at the 2023 ESMO Congress held in Madrid, Spain, from October 20-24, 2023. As of April 27, 2023, the study had enrolled 97 patients, including 39 with urothelial carcinoma and 29 with cervical cancer. The age range of the patients was 32-78 years (median age of 57 years), and the dosage ranged from 0.33 to 1.5 mg/kg. These subjects had previous treatments with platinum-based chemotherapy and immune checkpoint inhibitors. There were no treatment-related deaths in the study. Only one case of dose-limiting toxicity was observed in the 1.5 mg/kg group, which was grade 4 neutropenia lasting more than 5 days. The maximum tolerated dose (MTD) has not yet been reached. The incidence of any grade treatment-related adverse events (TRAEs) was 64.9%. The most common treatment-related adverse events were decreased white blood cell count (36.1%, 35/97), neutropenia (35.1%), nausea (22.7%), increased aspartate aminotransferase (22.7%), rash (19.6%), hair loss (19.6%), fatigue (18.6%), decreased appetite (18.6%), anemia (17.5%), vomiting (16.5%), and peripheral neuropathy (16.5%). The incidence of grade 3/4 TRAEs was 35.1%, with the most common being decreased white blood cell count (18.6%) and neutropenia (18.6%). On March 16, 2024, Mabwell (Shanghai) Bioscience announced at the Society of Gynecologic Oncology (SGO) Annual Meeting through a Focused Plenary Oral Presentation the positive clinical trial results of its Nectin-4 targeted ADC in cervical cancer. As of September 25, 2023, 92.50% (37/40) of the participants experienced treatment-related adverse events, with the most common grade 3 treatment-related adverse events being neutropenia at 40.00% (16/40), rash at 17.50% (7/40) and increased gamma-glutamyl transferase at 12.50% (5/40). There were no treatment-related deaths reported. Mabwell's ADC Pipeline Mabwell (Shanghai) Bioscience has developed two antibody-drug conjugates (ADCs), B7H3 ADC 7MW3711 and TROP2 ADC 9MW2921, based on its next-generation conjugation technology platform IDDC™. Both ADCs are currently in Phase I clinical trials. IDDC™ is a next-generation site-specific conjugation technology platform autonomously developed by Mabwell Bioscience, comprising of several systematic core patented technologies: the site-specific conjugation process DARfinity™, the site-specific linker IDconnect™, the novel payload molecule Mtoxin™, and the conditional release structure LysOnly™. The next-generation ADCs developed using these systematic patented technologies exhibit improved structural uniformity, quality stability, efficacy, and tolerance. The LysOnly™ technology enhances the tumor-specific release capacity of ADC drugs, reducing off-target effects. How to search for and analyze the development progress of ADC pharmaceuticals?If you want to learn about the latest developments in ADC drugs, you can use the drug search module of the Synapse database. This module supports searching for ADC drugs by classification through Targeting Moiety, Linker, and Payload. On the search results page, you can easily review information related to the ADC's technical category of the drugs. After clicking to enter the drug details page, you can also effortlessly obtain structural information about the ADC drug. Click on the image below to embark on a brand new journey of drug discovery!

At this conference, RemeGen's antibody-drug conjugates (ADCs) including Disitamab Vedotin and the mesothelin-targeting ADC RC88, will present 16 latest clinical research data across two innovative drugs, showcasing in 1 clinical science discussion, 5 poster presentations, and 10 online abstracts, and covering multiple cancer types such as stomach cancer, bladder cancer, and gynecological tumors. Disitamab Vedotin (RC48)Disitamab Vedotin (RC48) has been used for the treatment of gastric and urothelial carcinomas and received conditional approval in China in June and December of 2021 respectively. In August 2021, Seagen (now acquired by Pfizer) secured an exclusive global license (excluding Asia-Pacific) for Disitamab Vedotin in a deal worth up to $2.6 billion, which includes a $200 million upfront payment and up to $2.4 billion in milestone payments, along with royalties ranging from high single-digit percentages to above fifteen percent. The indications discussed at this meeting primarily focus on the effectiveness in recurrent or metastatic cervical cancer and muscle-invasive bladder cancer. According to data disclosed by the company at the CSCO Gynecological Cancer Annual Meeting in April this year, a Phase II, open-label, multi-center basket trial evaluated the efficacy and safety of RC48 monotherapy in HER2-expressing recurrent cervical cancer. In this trial, the RC48 dose was 2 mg/kg (Q2W). Among the 22 evaluable patients, the median progression-free survival (mPFS) was 4.37 months, the median duration of response (mDoR) was 5.52 months, and the one-year overall survival (OS) rate was 66%, particularly with a primary study endpoint objective response rate (ORR) reaching 36.4%. Subgroup analysis showed significant benefit in patients with HER2 IHC 1+ (ORR rate 50%), and RC48 also benefited those previously treated with anti-PD1, paclitaxel, and platinum therapy, showing impressive therapeutic efficacy in second-line and later treatments for recurrent cervical cancer. As for safety, the incidence of grade ≥3 treatment-related adverse events (TRAEs) was low, including decreased neutrophil count (12%), increased γ-glutamyl transferase (8%), and elevated alanine transaminase (8%). The overall safety profile was tolerable and controllable, with no ocular, pulmonary toxicity, or fatal TRAEs observed. Furthermore, for bladder cancer indications, based on previously disclosed data from the RC48-C005/C009 studies, Disitamab Vedotin in patients with previously failed chemotherapy for bladder cancer consistently achieves an objective response rate of 50.5%, with a median progression time of 5.9 months and a median survival time of 14.2 months, effectively extending patient survival. RC88RC88 is a mesothelin-targeted ADC (Antibody-Drug Conjugate) developed in-house by RemeGen. It is currently in Phase II clinical trials. RC88 utilizes RemeGen's innovative bridging technology for antibody-drug linkage, featuring a structure that includes a mesothelin-targeting antibody, a cleavable linker, and the small molecule cytotoxin MMAE (monomethyl auristatin E). This design allows for targeted binding to MSLN-positive tumor cells, facilitating the internalization of the antibody and effectively delivering the cytotoxin directly to cancer cells, thereby achieving substantial tumor-killing effects. The drug employs a disulfide bridge linker that offers a uniform Drug-to-Antibody Ratio (DAR) and maintains stable antibody protein structure, leading to higher efficacy and improved safety. In March 2023, an application for a Phase I/II clinical study of RC88 in combination with toripalimab for the treatment of patients with advanced malignant solid tumors was approved by China's CDE. In December 2023, an application for a Phase II clinical trial of RC88 in the treatment of gynecological tumors received approval from the U.S. FDA, and international multicenter clinical studies are set to commence across the United States, China, the European Union, and other regions. In January 2024, the FDA granted Fast Track Designation (FTD) to this drug for the treatment of patients with platinum-resistant recurrent epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer (PROC). How to search for and analyze the development progress of ADC pharmaceuticals?If you want to learn about the latest developments in ADC drugs, you can use the drug search module of the Synapse database. This module supports searching for ADC drugs by classification through Targeting Moiety, Linker, and Payload. On the search results page, you can easily review information related to the ADC's technical category of the drugs. After clicking to enter the drug details page, you can also effortlessly obtain structural information about the ADC drug. Click on the image below to embark on a brand new journey of drug discovery!